Motoko Y. Kimura
Thymocyte development, lineage decision, T cell homeostasis
Description of your research and your dream!
I always wondered why a unique precursor cell can differentiate into two distinctive features of cells with completely different function. The desire to unlock this mystery of mother nature drives my research. My research theme: “Mechanisms of Intrathymic T cell development” is the field of study, which fulfills my desire and teaches me a lot every single day. I wish, one day, that my research leads to the discovery of fundamental life phenomenon.
My main research question is: How do thymocytes acquire the self-recognition ability during their development and differentiate into different T cells that match with the types of a T cell receptor (TCR) expressed by an individual cell? During thymocyte development, immature thymocytes randomly rearrange their TCR and then express unique TCR to become mature T cells with different functions. The difference of the types of TCR lead to various kinds of T cells such as CD4T cells, CD8T cells, regulatory T cells, or NKT cells.
This may sound like common sense; however, it is actually a mysterious phenomenon, since all T cells come from common precursor and the trigger of differentiation is driven by signaling through the TCR. In fact, most of this mechanism is not fully understood. Furthermore, impairment of intrathymic T cell differentiation program is directly related to severe immunodeficiency diseases and/or development of autoimmune disorder. It would please me if I could discover the mechanism fundamental to life phenomenon which can be applied to the treatment of human diseases in the future.
- Biological Science & Technology, Tokyo University of Science
- Master Course, Graduate School of Biological Sciences, Tokyo University of Science
- Doctoral Course, Graduate School of Medicine, Chiba University (Prof. Toshinori Nakayama)
- PhD (Medical Science)
- Assistant Professor, Graduate School of Medicine, Chiba University (Prof. Toshinori Nakayama)
- Post-doctoral fellow, National Cancer Institute, NIH (Dr. Alfred Singer Lab)
- Researcher, National Cancer Institute, NIH (Dr. Alfred Singer Lab)
- Project Associate Professor, Graduate School of Medicine, Chiba University
- Associate Professor, Graduate School of Medicine, Chiba University
- *Kimura, M. Y., Igi, A., Hayashizaki, K., Mita, Y., Shinzawa, M., Kadakia, T., Endo, Y., Ogawa, S., Yagi, R., Motohashi, S., Singer, A., and Nakayama, T.: CD69 prevents PLZFhi innate precursors from prematurely exiting the thymus and aborting NKT2 cell differentiation. Nat. Commun. 9:3749 (2018). *Corresponding author
- *Kimura, M. Y., Thomas, J., Tai, X., Guinter, T. I., Shinzawa, M., Etzenperger, R., Li, Z., Love, P., Nakayama, T., and *Singer, A.: Timing and duration of MHC I positive selection signals are adjusted in the thymus to prevent lineage errors. Nat. Immunol. 17:1415-1423 (2016). *Co-corresponding author
- Luckey, M., Kimura, M. Y., Feigenbaum, L., et al: The transcription factor ThPOK suppresses Runx3 and imposes CD4+ lineage fate by inducing suppressors of cytokine signaling. Nat. Immunol. 15(7):638-45 (2014).
- Kimura, M. Y., Pobezinsky, L. A., Guinter, T. I., et al: IL-7 signaling must be intermittent, not continuous, during CD8+ T cell homeostasis to promote cell survival instead of cell death. Nat. Immunol. 14:143-151 (2013).
Japanese Society for Immunology, Japanese Cancer Association